The overall objective of this proposal is to evaluate irradiation as a modality for immunosuppression for bone marrow and organ transplantation across major histocompatability barriers. Emphasis will be on comparing various conditioning regimens employing total body (TBI) and total lymphoid (TLI) irradiation in mice. Certain regimens will also be combined with immunosuppressive drugs such as cyclophosphamide and methotrexate. We will also study irradiation conditioning in combination with serologic treatment of donor marrow grafts using monoclonal antibodies to eliminate populations of T cells which contribute to the development of graft versus host disease (GVHD). We will use antibodies directed against various T cell determinants to treat donor cells given to recipients conditioned by various regimens. Studies with irradiation will compare the efficacy of single dose versus fractionated dose irratiation. Moreover, we will evaluate high dose rate versus low dose rate relative to engraftment and GVHD potential. Such studies will optimize radiological immunosuppressive conditioning regimens relative to decreasing morbidity and mortality. In conditioning regimens which result in successful marrow engraftment, transplanted mice will be studied for immunocompetence employing immunological assays to measure certain in vivo and in vitro immunological responses. We will concentrate on determining T cell activities since T cells have been shown to contribute both to the development of GVHD and engraftment. Moreover, we may also obtain information related to the ontogeny of certain cell types in engrafted mice. We will also use engrafted mice to investigate the regulatory mechanisms whereby marrow grafts are accepted long-term without complications from GVHD or rejection. These studies will include a detailed investigation to determine the existence of an active suppressor cell mechanism in engrafted mice obtained by different conditioning regimens. These studies will provide a foundation for new and better conditioning regimens, provide comparisons of mechanisms of TBI versus TLI conditioned mice, and provide technical information which will be of great clinical value.